JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2019
·
IF 2.606
Yan-hong Wang,Ming Zhong,Lu Wang,Yu-liang Liu,Bin Wang,Yong Li
Chelerythrine (CHE) is an alkaloid with significant anticancer activity. However, CHE is required repeat administration to achieve the treatment effect due to its short half-life. To address this issue, a novel CHE controlled release drug delivery system consisted of composite magnetic-thermosensitive hydrogels (CMHs) with magnetocaloric properties was designed. The CMHs consisting of magnetic vinyl-Fe 3 O 4 @SiO 2 with good water dispersibility and crosslinking ability, and N-isopropylacrylamide-co-acrylamide copolymers , were synthesized by in situ polymerization. Vibrating sample magnetometer characterization verified that integration of vinly-Fe 3 O 4 @SiO 2 nanoparticles in the hydrogel network provided the sensitivity to magnetic fields. The CHE release experiment showed that the CMHs have temperature/magnetic field-triggered and sustained release properties, and the higher cumulative release amount could be achieved under higher temperature conditions or in the presence of an intermittent alternative magnetic field. It can be concluded that composite magnetic-thermosensitive hydrogels could be a potential anticancer drug delivery system with excellent thermotriggered release capabilities for CHE in magnetic hyperthermia.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
DOI
高影响因子
Microbial Drug Resistance
·
2021
·Vol. 27
·期 3
·337-341
·
IF 3.431
Mingzhi Wang,Bo Ma,Yunfeng Ni,Xiaoyan Xue,Mingkai Li,Jingru Meng,Xiaoxing Luo,Chao Fang,Zheng Hou
Multidrug resistance poses a severe threat to public health and urgently requires new solutions. The natural product chelerythrine (CHE) is a benzophenanthridine alkaloid with antimicrobial potential. In this study, CHE was effective against seven gram-positive bacterial strains, and the minimum inhibitory concentrations (MICs) ranged from 2 to 4 μg/mL. By contrast, CHE showed inferior antibacterial activities against 11 gram-negative strains, and the MICs varied from 16 to 256 μg/mL. We also determined the synergistic/additive effects of combining CHE with nine currently used antibiotics. CHE restored the antibacterial efficacy of the antibiotics against methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamases producing Escherichia coli. This study suggests that the combination of CHE with conventional antibiotics may be a promising strategy to combat infections caused by multidrug-resistant organisms.
研究领域:
微生物学
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药理学
·
感染病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Zhi-Ming Cui,Bo-Hang Zhou,Chao Fu,Liu Chen,Juan Fu,Fang-Jun Cao,Xin-Juan Yang,Le Zhou
Inspired by sanguinarine and chelerythrine, a novel antifungal 2-phenylphthalazin-2-ium scaffold as a simple analogue was designed. Most of the 30 compounds showed excellent inhibition activity against almost all eight phytopathogenic fungi, far superior to sanguinarine and chelerythrine. A third of the compounds were more active than azoxystrobin in most cases. Compounds 26 and 27 showed the highest total activity against all the fungi with EC50 means of ca. 4.6 μg/mL. Fusarium solani showed the highest susceptibility with an EC50 mean of 3.62 μg/mL to 19 compounds. A concentration of 25.0 μg/mL 27 can fully control the Colletotrichum gloeosporioides infection in apples over 9 days. Electron microscopic observations showed that 27 was able to damage the structures of the hypha and cell membrane. The structure–activity relationship showed that the presence of electron-withdrawing groups on the C-ring increases the activity against most of the fungi. Thus, 2-phenylphthalazin-2-ium compounds represent promising leads for the development of novel fungicides.
研究领域:
药理学
·
植物保护学
·
有机化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCES IN POLYMER TECHNOLOGY
·
2020
·
IF 1.539
Yunlong Liu,Jie Guo,Zhuobing Xiao,Dazhao Peng,Ke Song
Separation and purification of active components from biomass by inorganic materials during the pretreatment process of hydrothermal conversion are studied in this work. The batch experiment results show that an initial solution pH of 6 favors chelerythrine adsorption, and the optimum adsorbent dosage is 2.0 g. The adsorption mechanism of ZSM-5 for chelerythrine is investigated by adsorption kinetics, isotherm adsorption models, and thermodynamics analysis. The results show that the kinetics data fit the pseudo-second-order model well (R2 = 0.9991), and the intraparticle diffusion model has 3 diffusion stages, preliminarily indicating that chemisorption plays a major role in the adsorption process, and the sorption mechanism includes intraparticle, external, and boundary diffusion. The adsorption isotherms agree well with the Langmuir model, indicating the occurrence of monolayer molecular adsorption during the adsorption process. Meanwhile, the maximum adsorption capacity is 2.327, 2.072, and 1.877 mg/g at different temperatures (288 K, 298 K, and 308 K), respectively. The thermodynamic data demonstrate that the adsorption process is exothermic and spontaneous in nature. These observed results clearly confirm that ZSM-5 has potential superior properties for the enrichment and purification of alkaloids during the pretreatment of biomass.
研究领域:
生物化学
·
环境科学
·
材料科学
✓ 已验证
DOI
高影响因子
Engineering
·
2023
·
IF 12.8
Huangwei Song,Xueyang Wang,Muchen Zhang,Zhiyu Zou,Siyuan Yang,Tian Yi,Jianfeng Wang,Dejun Liu,Yingbo Shen,Chongshan Dai,Zhihai Liu,Timothy R. Walsh,Jianzhong Shen,Congming Wu,Yang Wang
The emergence and spread of the mobile colistin-resistance gene, mcr-1 , and its variants pose a challenge to the use of colistin, a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant (XDR) Gram-negative pathogens. Antibiotic adjuvants are a promising strategy to enhance the efficacy of colistin against colistin-resistant pathogens; however, few studies have considered the effects of adjuvants on limiting resistance-gene transmission. We found that chelerythrine (4 mg∙L −1 ) derived from Macleaya cordata extract, which is used as an animal feed additive, reduced the minimal inhibitory concentration (MIC) of colistin against an mcr-1 positive E. coli strain by 16-fold (from 2 to 0.125 mg∙L −1 ), eliminated approximately 10 4 colony-forming units (CFUs) of an mcr-1 -carrying strain in a murine intestinal infection model, and inhibited the conjugation of an mcr-1 -bearing plasmid in vitro (by >100-fold) and in a mouse model (by up to 5-fold). A detailed analysis revealed that chelerythrine binds to phospholipids on bacterial membranes and increases cytoplasmic membrane fluidity, thereby impairing respiration, disrupting proton motive force (PMF), generating reactive oxygen species (ROS), and decreasing intracellular adenosine triphosphate (ATP) levels, which subsequently downregulates mcr-1 and conjugation-associated genes. These dual effects of chelerythrine can expand the use of antibiotic adjuvants and may provide a new strategy for circumventing mobile colistin resistance.
研究领域:
微生物学
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药理学
·
抗菌素耐药性
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传染病学
✓ 已验证
产品关联
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2019
·
IF 3.775
Yizhong Shen,Chunlei Zhu,Yaping Wang,Jingjing Xu,Ruyu Xue,Fuyun Ji,Yiwei Wu,Zeyu Wu,Wencheng Zhang,Zhi Zheng,Yingwang Ye
Chelerythrine (CHE), a benzophenanthridine alkaloid , is usually used as a nutritional and functional additive in variety of health foods . However, it should be paid enough attention because of its potential toxicity to human health. In this work, the binding mechanism of CHE with bovine serum albumin (BSA) was systematically investigated with spectroscopic approaches. The results showed that the mixture of BSA with CHE could spontaneously cause the formation of BSA-CHE complex through electrostatic interaction under simulative physiological conditions (0.01 mol L −1 Tris-HCl, 0.015 mol L −1 NaCl, pH = 7.4). Site marker competitive displacement experiments exhibited that CHE was primarily bound to the hydrophobic pocket of the site II (subdomain IIIA) of BSA. It has been reported that the binding of small functional molecules to serum albumins remarkably impacts their absorption, distribution, metabolism, conformation, and excretion features. Therefore, this study might be helpful for human to have an in-depth understanding of the biological effect of CHE in vivo and guide human to take it safely and reasonably.
研究领域:
生物化学
·
毒理学
·
药理学
✓ 已验证
DOI
高影响因子
TALANTA
·
2015
·
IF 3.545
Yue Sun,Yuanyuan Li,Jiajian Zeng,Qixian Lu,Paul C.H. Li
A new method has been developed for separation of chelerythrine and sanguinarine in medicinal plants used in traditional Chinese medicine (TCM). The separation is achieved by microchip electrophoresis (CE) using laser-induced fluorescence detection. The CE separation is achieved by using a hydro-organic medium as the electrolyte buffer. The experimental results are consistent with the prediction by theory in terms of resolution and migration speed because of the low Joule heat generated in microchip CE . In addition, formamide was found to have a potential for separation of molecules with similar chemical structures. Based on these findings, a run buffer containing 50% formamide was used to separate chelerythrine (CHE) and sanguinarine (SAN). The influencing factors, such as solvent of run buffer, pH of buffer, separation distance, and separation voltage, were optimized. Baseline separation of chelerythrine and sanguinarine was achieved within 120 s under an electrical voltage of 1.8 kV. Good linearity was observed in the concentration range of 0.15–550 μg mL −1 ( r =0.9993) for CHE and in the range of 0.3–600 μg mL −1 ( r =0.9998) for SAN. A low limit of detection (LOD) was achieved because of the high sensitivity achieved by laser-induced fluorescence detection (i.e. 5.0 ng mL −1 and 2.0 ng mL −1 for CHE and SAN, respectively). The contents of CHE are found to be 641.8±7.5 and 134.0±2.3 mg/kg in extracts of Macleaya cordata and Chelidonium majus , respectively, with good recovery of above 99%. The corresponding values for SAN found in these Chinese herbal extracts are 681.8±7.9 mg/kg and 890.5±8.9 mg/kg, respectively.
研究领域:
分析化学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Future Microbiology
·
2020
·
IF 2.907
Ying Gong,Siwen Li,Weixin Wang,Yiman Li,Wenli Ma,Shujuan Sun
Aim: To evaluate whether chelerythrine (CHT) exhibited antifungal activity against Candida albicans in vitro and in vivo and to explore the underlying mechanisms. Materials & methods: Broth microdilution assay and Galleria mellonella model were used to evaluate the antifungal effect in vitro and in vivo, respectively. Mechanism studies were investigated by morphogenesis observation, Fluo-3/AM, DCFH-DA and rhodamine6G assay, respectively. Results: CHT exhibited antifungal activity against C. albicans and preformed biofilms with minimum inhibitory concentrations ranged from 2 to 16 μg/ml. Besides, CHT protected G. mellonella larvae infected by C. albicans. Mechanisms studies revealed that CHT inhibited hyphal growth, increased intracellular calcium concentration, induced accumulation of reactive oxygen species and inhibited drug transporter activity. Conclusion: CHT exhibited antifungal activity against C. albicans.
研究领域:
微生物学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ANALYST
·
2019
·Vol. 144
·期 13
·4081-4085
·
IF 4.019
Yuan-Min Liu,Xiu-Yu Fang,Fang Fang,Zhi-Yong Wu
Chelerythrine (CHE) is one of the potential drugs for cancer treatments. The interaction between hairpin DNA and CHE has been investigated by spectral and mass spectrometry methods. In this paper, the stability of hairpin DNA with different loop bases and its interaction with CHE were explored with a single α-hemolysin (α-HL) nanopore sensing interface. The results showed that the characteristic current pulses not only relate to the loop composition changes of the hairpin DNA, but also provide interaction information between CHE and the hairpin DNA molecules. The dwell time of current pulses for hairpin DNA was significantly increased (hundreds of ms) due to the addition of CHE, and two characteristic current distributions were recognized for the hairpin with T3 and C3 loops. The two characteristic current groups could be ascribed to the hairpin DNA and the ones with CHE. This study indicates that it is possible to study the interaction between single CHE and single hairpin DNA molecules by the single-nanopore sensing interface as an alternative method to conventional spectrometric methods for therapeutic mechanism and drug screening purposes.
研究领域:
生物物理
·
分子生物学
·
纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2022
·
IF 4.345
Songjiang Wu,Yanying Yang,Feiping Li,Lifu Huang,Zihua Han,Guanfu Wang,Hongyuan Yu,Haiping Li
Introduction Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE), a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in prostate cancer cells were studied for the first time.Methods In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis.Results Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE.Conclusion Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Antioxidants
·
2025
·Vol. 14
·期 9
·1063
·
IF 6.6
Jinlong Liu,Yanfei Zhang,Hao Wu,Pan Yang,Wenlong Wang,Chenliang Li,Hong Cao,Jinying Wu,Xin Sun
Chelerythrine (CHE) is the main active component ofChelidonium majusL., possessing excellent antioxidant and anti-inflammatory properties. However, the protective effects of CHE against liver injury and its underlying mechanisms remain unclear. We aimed to investigate the effects of CHE on acute liver injury (ALI) and explore its underlying mechanisms. Mice were orally administered with or without CHE (15 and 30 mg/kg) treatment for 7 days, followed by a single intraperitoneal injection of acetaminophen (APAP, 350 mg/kg). After 24 h, serum, liver, and fecal samples were collected. Then, 16S rRNA gene sequencing, metabolomics, and transcriptomics approaches were employed to investigate the protective effects of CHE against ALI. Finally, we elucidated the role of CHE in restoring gut microbiota and metabolic disorders in the context of ALI. The results showed that CHE significantly inhibited ALT and AST levels (p< 0.001). Furthermore, CHE counteracted APAP-induced alterations in IL-6, IL-1β, TNF-α, MPO, MDA, H2O2, CAT, SOD, and GSH (p< 0.05). These results indicate that CHE possesses antioxidant properties and inhibits inflammatory factors, thereby protecting the organism from APAP-induced ALI. CHE treatment significantly altered gut microbiota composition, particularly increasing levels of the beneficial bacteriumBarnesiella intestinihominis(p< 0.05). In addition, CHE reversed metabolic disturbances and inhibited oxidative and inflammatory signaling pathways. These findings suggest that CHE is a natural hepatoprotective agent that prevents ALI by modulating gut microbiota, related metabolites, oxidative stress, and inflammation. This study provides new insights into CHE as a potential therapeutic approach for ALI.
研究领域:
药理学
·
毒理学
·
微生物组研究
·
系统生物学
·
代谢组学
·
转录组学
·
肝脏病学
·
天然产物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2018
·
IF 3.234
Bo Shi,Shixing Li,Hao Ju,Xin Liu,Dan Li,Ying Li
The present study aimed to evaluate the renoprotective effects of chelerythrine (CHE), a protein kinase C inhibitor, on neonatal rats after partial unilateral ureteral obstruction (UUO) surgery. New born Sprague Dawley rats were subjected to partial UUO 48 h after birth and received a daily intraperitoneal injection of 5 mg/kg CHE. At 21-day age, the rats were scarified and the kidneys were collected for analysis. Results showed that CHE treatment significantly increased kidney weight and restored renal function in the obstructed kidney. Histological examination demonstrated that CHE attenuated renal injury by reducing renal parenchymal loss and preventing glomerular and tubular degeneration. In addition, CHE inhibited partial UUO-induced upregulated kidney injury molecule-1 expression and apoptosis and renal fibrosis. Moreover, as a PKC inhibitor, CHE significantly inhibited PKCα and PKCβ membrane translocation. This action may be associated with its effects of anti-apoptosis and anti-fibrosis and contribute to the renoprotection. This short-term study suggests that CHE is beneficial for obstructive nephropathy in neonatal rats and provides foundation for further studies to reveal the long-term effects of CHE on obstructive nephropathy in children and infants.
研究领域:
药理学
·
肾脏病学
·
儿科学
✓ 已验证
DOI
PubMed
高影响因子
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